Lm infection has been a reportable disease in Israel since 1993. A preliminary report from the Ministry of Health (MOH) claimed a fivefold increase in incidence from 1996 to 1998, but the information was incomplete (
Of the 24 general (acute-care) hospitals in Israel, 11 are large, with 500-1,200 beds, 8 have 300-499 beds, and 5 have <300 beds. Information on Lm infections was collected by contacting infectious disease specialists in each of the 19 larger hospitals. The specialists were asked to identify retrospectively all patients with listeriosis (as defined below) from the period 1995-1999 in their hospitals and to complete a questionnaire on each. Questionnaires were completed from 17 of the hospitals (11 large, 6 intermediate), and complementary information was retrieved from the MOH passive and active surveillance files on 4 additional hospitals (1 intermediate and 3 small). These 21 hospitals represented approximately 95% of the total acute-care beds in Israel during the study period.
One hundred sixty-one patients with Lm infection were identified. Clinical information was available for all patients except five (3%: two with positive blood cultures and one with a positive vaginal culture who were not hospitalized, and two with positive blood cultures whose hospital charts could not be retrieved).
Lm isolates were identified by standard methods in the microbiology laboratory in each medical center, then sent to the Reference Laboratory for Listeria in Jerusalem for confirmation.
Listeriosis was defined as the growth of Lm (as confirmed at the reference laboratory) from any body site. An infection in a pregnant woman and her fetus or neonate was considered a single perinatal event.
We conducted aPubmed search for studies describing nonselective, population-based surveys of Lm infections in the English language literature of the last decade (1990-2000). All case series describing at least 15 nonperinatal, nongastroenteritis infections were included in the review of nonperinatal listeriosis. All case series describing at least 15 perinatal cases were included in the review of perinatal listeriosis.
The 161 cases identified during the 5-year study period included 91 (57%) nonperinatal and 70 (43%) perinatal infections. The average annual incidence during the study period was 0.6/100,000 population. The marked increase in 1998 (
Number of cases of perinatal and nonperinatal
Seasonal occurrence of
The mean age of the 87 nonperinatal cases with available clinical information was 67 years (range 4-91), 66 (76%) were ≥60 years of age (
Age distribution of 87 nonperinatal cases of
| Main underlying illness | No. of cases | Additional underlying conditions | ||||
|---|---|---|---|---|---|---|
| Steroids/ chemotherapy | Chronic renal failure | Chronic liver disease | Diabetes mellitus | Others | ||
| Hematologic malignancy | 23 | 19 | 3 | 2 | 7 | 8a |
| Solid malignancy | 22 | 9 | ||||
| Chronic renal failure | 8b | 1 | 2 | 1c | ||
| Chronic liver disease | 8 | 1 | 1 | 2c | ||
| Diabetes mellitus | 3 | 1 | ||||
aSplenectomy (2 cases) neutropenia (
Clinical syndromes in the 87 nonperinatal cases were primary bacteremia in 41 (47%), meningitis in 24 (28%), bacteremia with a focal infection in 18 (21%), and focal infection without bacteremia in 4 (5%) (
| Clinical syndrome | Immunocompromised | Immunocompetent | Total |
|---|---|---|---|
| Bacteremia without focus | 34 (53%) | 7 (30%) | 41 (47%) |
| Meningitis | 17a (27%) | 7 (30%) | 24 (28%) |
| Bacteremia with focus | 9b (14%) | 9c (39%) | 18 (21%) |
| A focus without bacteremia | 4d (6%) | 0 | 4 (5%) |
| Total | 64 (100%) | 23 (100%) | 87 (100%) |
a With bacteremia (6 cases), with pneumonia (1 case).
b Endocarditis (3 cases), peritonitis (
The case-fatality rate in the nonperinatal group was 38% (33 of 87). Twelve of the 33 deaths occurred within 48 hours of admission or disease onset. We observed a lower mortality rate (6 [19%] of 31) among persons who received a penicillin (mostly ampicillin) as empiric therapy, compared with those who received a penicillin only after culture results were reported (9 [30%] of 30), but this difference was not statistically significant (p=0.25). The difference in death rates in immunocompromised (28 [44%] of 64) compared with immunocompetent patients (5 [22%] of 23) had borderline statistical significance (p=0.05). There was no correlation between death and age for the whole group; however, all five immunocompetent patients who died were >80 years of age.
Clinical information was available on 69 pregnant women (mean age 28 years; range 21-40 years) and their offspring. Twenty-seven pregnancies (gestational age 9-26 weeks) resulted in intrauterine fetal death and miscarriage, one full-term infant was stillborn, and three others (born at 26, 29, and 39 weeks) died within 24-48 hours of birth (
| Mothers’ cultures | Infants’ cultures | ||||||
|---|---|---|---|---|---|---|---|
| Type of mother-infant infection | No. of cases | Blood only | Blood and tissue | Tissue only | Blood only | Blood and tissue | Tissue only |
| Uninfected mother and infected infant | 13 (19%) | 4 | 7 (3) | 2 (2) | |||
| Infected mother and infected infant | 9 (13%) | 2 | 1 | 6 | 3 | 2 | 4 (1) |
| Infected mother and uninfected infant | 16 (23%) | 9 | 3 | 4 | |||
| Fetal/neonatal death (amnionitis) | 31a (45%) | 4 | 13 | 14 | 1 | 1 (1) | |
| Total | 69 (100%) | 54 | 24 | ||||
aIncludes 27 intrauterine deaths with abortions, 1 stillbirth, and 3 early neonatal deaths. Numbers in parenthesis are cases of meningitis. Tissue denotes any material that is not blood, such as cerebrospinal fluid, placenta, and amniotic fluid.
The other 38 mothers gave birth to live infants, 16 of whom had no evidence of Lm infection. Eleven of the 16 uninfected infants were delivered when the mothers had active Lm amnionitis (gestational ages 25 to 40 weeks), and 5 were delivered several weeks after the maternal infection, which occurred at weeks 19, 21, 35, 36, and 37. Twenty-two infants had evidence of Lm infection after birth, 18 within 48 hours of delivery and 4 on days 4-8. Only two (11%) of the 18 infants with early infection had meningitis, compared with all 4 with later onset of infection.
All infected mothers had mild illness and recovered uneventfully; none had meningitis. One mother had an underlying immunocompromising condition (systemic lupus erythematosus).
Nine case-series of nonperinatal listeriosis and five case-series of perinatal infection matched the inclusion criteria. These reports and our study provided 1,250 cases of nonperinatal and 494 cases of perinatal listeriosis for analysis (
| First author, year (ref) | |||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|
| Characteristic | McLauchlin, 1990 ( | Gellin, 1991 ( | Cherubin, 1991 ( | Skogberg, 1992 ( | Nolla-Salas, 1993 ( | Jones, 1994 ( | Paul, 1994 ( | Bula, 1995 ( | Goulet, 1996 ( | Siegman-Igra, 2001 (present study) | Total or average |
| Country and scope | England, national | USA, six areas | USA, four centers | Finland, Helsinki | Spain, Barcelona | England, Bristol | Australia, Sydney | Switz-erland, western part | France, national | Israel, national | Worldwide |
| Study period | 1967-1985 | 1986 | 1982-1999 | 1971-1989 | 1990 | 1983-1992 | 1983-1992 | 1983-1997 | 1992 | 1995-1999 | 1967-1999 |
| Total no. of cases | 722 | 246 | 119 | 74 | 31 | 29 | 84 | 122 | 225a | 156 | 1,808 |
| Nonperinatal cases (% of total) | 474 (66%) | 179 (73%) | 54 (45%) | 58 (78%) | 29 (94%) | 16 (55%) | 71 (85%) | 57 (47%) | 225 (NA) | 87 (56%) | 1,025/1583 (65%) 1,025+225=1,250 |
| Mean age (range) (years) | 59 (1-97) | NA (<1-95) | NA | 50 (29-66) | 58 (17-89) | 60 (1-95) | 39% (>60) | 66 (31-96) | 65 (1-101) | 67 (4-91) | 50-67 |
| Male gender | 265 (58%) | 101 (56%) | NA | NA | 24 (77%) | 9 (56%) | NA | 33 (58%) | 135 (62%) | 56 (64%) | 623 (60%) |
| Peak season | Autumn and spring | Late spring to fall | May-Aug | NA | 39% in July-Sept | 76% in July-Dec | NA | NA | NA | 70% in May-Oct | Summer and fall |
| Annual incidenceb | NA | 0.7 | NA | 0.09 - 0.65 | 1.1 | 0.35 | 0.3 | NA | NA | 0.6 | 0.1-1.1 |
| Immunocompromised | 261/337 (77%) | NA | 53/54(98%) | 47/58(81%) | 24/29 (83%) | 13/16 (81%) | 59/71 (83%) | 25/57 (42%) | 159/225(71%) | 64/87 (74%) | 705/934 (74%) |
| CNS infection | 268/474 (57%) | 55/179 (31%) | 19/54 (35%) | 29/58 (50%) | 9/31 (29%) | 6/16 (37%) | 29/71 (41%) | 45/57 (79%) | 110/224(49%) | 24/87 (28%) | 594/1,251 (47%) |
| Bacteremia | 183/474 (39%) | 119/179 (66%) | 35/54 (65%) | 24/58 (41%) | 20/31 (65%) | 10/16 (73%) | 40/71 (56%) | 12/57 (21%) | 97/224 (43%) | 59/87 (68%) | 599/1,251 (48%) |
| Focal disease onlyd | 9/474 (5%) | 5/179 (3%) | - | 5/58 (8%) | 2/31 (6%) | - | 2/71 (3%) | - | 17/224 (8%) | 4/87 (5%) | 44/1,124 (4%) |
| Mortality | 164/371 (44%) | 63/179(35%) | 17/54(31%) | 15/58(26%) | 16/31 (52%) | 6/16 (37%) | 27/71 (38%) | 18/57 (32%) | 54/225 (24%) | 33/87 (38%) | 413/1,149 (36%) |
aIncludes nonperinatal cases only. bEstimated annual incidence per 105 population. cBacteremia with or without a non-CNS focus of infection (e.g., pneumonia, endocarditis, urinary tract infection, prostatitis, peritonitis, gastroenteritis, rectal abscess, osteomyelitis, and cellulitis). dFor example, peritonitis, pleuritis, arthritis, pericarditis, cholecystitis, appendicitis, and cellulitis. NA= not available; CNS= central nervous system.
| First author, year (ref) | |||||||
|---|---|---|---|---|---|---|---|
| Characteristic | McLauchlin, 1990 ( | Gellin, 1991 ( | Cherubin, 1991 ( | Craig,
1996 ( | Nolla-Salas,
1998 ( | Siegman-Igra, 2001 (present study) | Total or average |
| Country and region | England, national | USA, six areas | USA, four centers | Australia, Melbourne | Spain, Barcelona | Israel, national | Worldwide |
| Study period | 1967-1985 | 1986 | 1982-1999 | 1983-1994 | 1990-1996 | 1995-1999 | 1967-1999 |
| Total no. of cases | 722 | 246 | 119 | 24a | 135 | 156 | 1,400 |
| Perinatal infection (% of total) | 248 (34%) | 67 (27%) | 65 (55%) | 24 (NA) | 21 (16%) | 69 (44%) | 470/1,378 (34%) 470+24=494 |
| Estimated incidence per 104 births | NA | 0.8-2.4 | NA | 2 | 0-4.1 | 1.4 | 0.6-4.1 |
| Average maternal age (range) (years) | NA | 26 (17-35) | NA | NA (18-39) | 30 (26-34) | 28 (21-40) | NA (26-30) |
| Early neonatal infection and survival | 114b (46%) | 31 (46%) | 20 (31%) | 14c (58%) | 11 (52%) | 19 (28%) | 209/494 (42%) |
| Late neonatal infection and survival | 36d (15%) | 8e (12%) | 21(32%) | 1d (5%) | 3d (4%) | 69/494 (14%) | |
| Infected mother and uninfected infant | 9 (4%) | 13 (19%) | 2 (3%) | 4 (17%) | 5 (23%) | 16 (23%) | 49/494 (10%) |
| Intrauterine death | 42 (17%) | 14 (21%) | 15 (23%) | 4 (17%) | 3 (14%) | 28 (41%) | 106/494 (21%) |
| Postnatal death | 47 (19%) | 1 (1%) | 7 (11%) | 2 (8%) | 1 (5%) | 3 (4%) | 61/494 (12%) |
| Gestational age at abortion (weeks) | 12-28 | 11-30 | NA | 18-29 | 10-27 | 9-26 | 9-29 |
| Immunocompromised mothers | 5 | 1 | 1 | 1 | 8f | ||
aIncludes only perinatal cases. bIncluding 29 with unknown time of onset. cNo differentiation between early and late neonatal infection. d>5 days. e>7 days. f2 diabetes mellitus, 2 renal transplant, 2 systemic lupus erythematosus, 1 Crohn disease and steroids, 1 HIV infection. NA= not available
Most (74%) of the persons affected in the reported cases (
With regard to clinical syndromes, the most common (47%) site of infection was the central nervous system (CNS) (
Perinatal infection constituted 34% (470 of 1,378) of cases among studies that supplied this information (
Two hundred seventy-eight (56%) live-born infants had neonatal listeriosis and survived. Most of this neonatal infection was of early onset (209 cases), but the definition of early onset varied (from ≤5 to ≤7 days), and information concerning day of onset was incomplete in some series (
Ingestion of Lm is a very common occurrence (
The case-fatality rate in the collected data on perinatal infection was 36% (413 of 1,149 patients for whom this information was available). This high mortality reflects both the severity of Lm infection and the seriousness of the underlying conditions. Higher mortality rates were correlated with older age, presence of CNS infection, and immunodeficiency (
An unexpected observation in our study was the occurrence of hospital-acquired listeriosis in adults. The presumed hospital acquisition occurred on day 3-67 of hospital stay in 59 (16%) of 369 cases with relevant information, as reported in four studies, including ours (
Among perinatal infections, we report the highest case-fatality rate (45%). This observation could be related to the frequency of taking cultures from aborted tissues. The diagnosis of Lm can easily be missed if cultures are not routinely taken from aborted fetal tissues or if blood (and other) cultures are not obtained from febrile pregnant women. The great variability in incidence rates and other epidemiologic features between studies and among medical centers within studies suggests that many cases escaped diagnosis.
Concerning the mothers, all authors described a mild febrile “influenzalike” illness, without maternal deaths. Only one of the 494 mothers had meningoencephalitis with Lm isolated from the cerebrospinal fluid, but underlying condition or maternal and fetal outcomes were not reported (
In conclusion, listeriosis is an emerging zoonosis that constitutes a life-threatening disease for human fetuses and neonates, the elderly, and patients with certain predisposing conditions. Documented cases may not represent the true incidence in the community, especially with regard to perinatal infection. Fetal and maternal cultures should be obtained in every case of spontaneous abortion or stillbirth, to ensure proper diagnosis. Empiric ampicillin therapy should be included in the treatment of neonatal meningitis, sepsis, or meningitis in the elderly and immunocompromised patients and in febrile pregnant women without a source of infection.
Suggested citation: Siegman-Igra Y, Levin R, Weinberger M, Golan Y, Schwartz D, Samra Z, et al.
Dr. Lang died November 18, 2001.
We thank Esther Eshkol for editorial assistance.
Dr. Siegman-Igra is head of the Infectious Diseases Unit at the Tel-Aviv Sourasky Medical Center and Professor of Medicine at the Sackler School of Medicine, Tel-Aviv University. Her main research interests are bacteremic infections, nosocomial infections, hospital epidemiology, and the epidemiology of infectious diseases in Israel.